The proposed research is a continuation of attempts to elucidate the biochemical nature and physiologic significance of a humoral factor in plasma of volume expanded dogs which inhibits sodium transport in toad bladder (antinatriferic activity) (AA) and is natriuretic in rats. Evidence has been accumulated which suggests that this factor may be a natriuretic hormone. These studies have been extended to a second factor which is natriuretic in rats but which does not have AA. This factor has a higher molecular weight than the factor with AA. Recent studies have indicated that both of these factors are produced by enzymatic action from precursors, suggesting that "natriuretic hormone" is a cascading system. Studies are outlined to isolate, purify and identify the several components of this cascade. High pressure liquid chromatography combined with a fluorescent detection system will be utilized. Column effluents reacted with fluorescamine form peptide fluorophors. This procedure allows detection of picomole concentrations of peptides and amino acids. Isolation of these compounds will allow further studies of their physiologic and pathophysiologic significance. Micropuncture studies will be performed to determine their site of action in the nephron.